11-117986352-T-C

Position:

• chr11-117986352-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 11-117986352-T-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 997,590 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (35 hom.)
• Consequence: IL10RA NM_001558.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963

Genes affected

IL10RA (HGNC:5964): (interleukin 10 receptor subunit alpha) The protein encoded by this gene is a receptor for interleukin 10. This protein is structurally related to interferon receptors. It has been shown to mediate the immunosuppressive signal of interleukin 10, and thus inhibits the synthesis of proinflammatory cytokines. This receptor is reported to promote survival of progenitor myeloid cells through the insulin receptor substrate-2/PI 3-kinase/AKT pathway. Activation of this receptor leads to tyrosine phosphorylation of JAK1 and TYK2 kinases. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4			upstream_gene_variant		ENST00000227752.8	NP_001549.2
IL10RA	XM_047426882.1			upstream_gene_variant			XP_047282838.1
IL10RA	NR_026691.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8			upstream_gene_variant		1	NM_001558.4	ENSP00000227752	P1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2407 AN: 152060 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00317 AC: 242 AN: 76282 Hom.: 4 AF XY: 0.00224 AC XY: 92 AN XY: 41156

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000694

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00150 AC: 1270 AN: 845412 Hom.: 35 Cov.: 11 AF XY: 0.00131 AC XY: 565 AN XY: 430370

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000171

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000453

Gnomad4 OTH exome AF: 0.00369

GnomAD4 genome AF: 0.0158 AC: 2405 AN: 152178 Hom.: 56 Cov.: 33 AF XY: 0.0153 AC XY: 1137 AN XY: 74402

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.000702 Hom.: 1

Bravo AF: 0.0179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7925112; hg19: chr11-117857067;